Influence of curcumin in combination with cisplatin on the invasion and metastasis of lung cancer A549 cells and its possible mechanisms_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

XIA Yezhou ,  TAN Xiaowu , ZENG Saili

Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P. R. China;

Corresponding?author：

TAN Xiaowu, Email: tanxiaowu1970@163.com

Keywords：

Curcumin; Cisplatin; Lung cancer; Invasion and metastasis

DOI：

10.7507/1671-6205.201706015

Video：

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Objectives To explore the effects of curcumin and cisplatin on A549 lung cancer cell invasion and metastasis, and explore the influence of the two drugs on matrix metalloproteinase 9 (MMP-9) and E-cadherin protein. Methods MTT assay was performed to detect the effects of curcumin, cisplatin alone and the combination on A549 lung cancer cell proliferation. Transwell assay was performed to detect the effects of curcumin, cisplatin alone and the combination on the invasion and metastasis of lung cancer cells. Western blot was used to detect the protein expression of MMP-9 and E-cadherin. Results The proliferation inhibition of A549 lung cancer cell rate in 5, 10, 20, 40 μmol/L of curcumin was 6.50%±1.06%, 11.70%±0.88%, 22.97%±0.82%, 27.93%±0.94%, respectively. Compared with control group, the proliferation inhibition rates in four different curcumin groups were significantly increased (all P<0.01). The differences in the proliferation inhibition rates among four different curcumin groups were statistically significant (allP<0.05). The proliferation inhibition rates of A549 lung cancer cell in 1, 2, 4 mg/L of cisplatin were 7.12%±0.86%, 20.07%±1.14%, 26.88%±0.51%, respectively. Compared with control group, the proliferation inhibition rates in three different cisplatin groups were significantly increased (allP<0.01). The differences in the proliferation inhibition rates among three different cisplatin groups were statistically significant (allP<0.01). The proliferation inhibition rates of A549 lung cancer cell in curcumin (20 μmol/L) combined with cisplatin (1, 2, 4 mg/L respectively) were 28.37%±0.57%, 39.72%±0.64%, 46.27%±0.86%, respectively. Compared with control group and curcumin or cisplatin used alone, the proliferation inhibition rates of three combined groups were significantly increased (allP<0.01). The invasion inhibition rates of A549 lung cancer cell in curcumin group (20 μmol/L), cisplatin group (2 mg/L) and combined group (curcumin 20 μmol/L plus cisplatin 2 mg/L) were 38.62%±0.23%, 36.52%±0.33%, 63.78%±0.59%, respectively. Compared with control group and curcumin or cisplatin used alone, the invasion inhibition rates of combined group were significantly increased (allP<0.01). The protein grey values for curcumin group (20 μmol/L), cisplatin group (2 mg/L) and combined group (curcumin 20 μmol/L plus cisplatin 2 mg/L) were 0.768±0.047, 0.654±0.104, 0.684±0.008, 0.444±0.104 (MMP-9) and 0.603±0.170, 0.792±0.050, 0.784±0.045, 0.879±0.110 (E-cadherin), respectively. Compared with control group and curcumin or cisplatin used alone, the protein grey values of combined group were significantly different (allP<0.01 orP<0.05). Conclusions Curcumin and cisplatin combination can inhibit the invasion and metastasis of lung cancer A549 cells. Its mechanism may be related to downregulating MMP-9 and upregulating E-cadherin.

Citation： XIA Yezhou, TAN Xiaowu, ZENG Saili. Influence of curcumin in combination with cisplatin on the invasion and metastasis of lung cancer A549 cells and its possible mechanisms. Chinese Journal of Respiratory and Critical Care Medicine, 2017, 16(6): 581-585. doi: 10.7507/1671-6205.201706015 Copy

1.	陳萬青, 張思維, 鄭榮壽, 等. 中國惡性腫瘤發病和死亡分析. 中國腫瘤, 2013, 22(1): 2-12.
2.	徐煒, 陳清勇, 陳方園. LIMK-1/COFILIN 在姜黃素抑制人肺癌細胞增殖和轉移中的作用. 實用腫瘤雜志, 2014, 29(1): 36-40.
3.	Nautiyal J, Banerjee S, Kanwar SS, et al. Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells. Int J Cancer, 2011, 128(2): 951-961.
4.	Teiten MH, Gaascht F, Cronauer M, et al. Anti-proliferative potential of curcumin in androgen-dependent prostate cancer cells occurs through modulation of the Wingless signaling pathway. Int J Oncol, 2011, 38(1): 603-611.
5.	Mimeault M, Batra SK. Potential application of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy. Chin Med, 2011, 23(1): 31-37.
6.	Fan CC, Wang TY, Cheng YA, et al. Expression of E-cadherin, Twist, and P53 and their prognostic value in patients with oral squamous cell carcinoma. J Cancer Res Clin Oncol, 2013, 139(10): 1735-1744.
7.	Zhong YC, Zhang T, Di W, et al. Thrombin promotes epithelial ovarian cancer cell invasion by inducing epithelial-mesenchymal transition. J Gynecol Oncol, 2013, 24(3): 265-272.
8.	崔若凡, 張寶剛, 姬靜, 等. ARK5、MMP-2 和 MMP-9 在胃癌中的表達及與侵襲轉移的關系. 實用醫學雜志, 2012, 28(7): 1073-1076.
9.	李登欣, 李石. E-鈣粘素、γ-連環素及基質金屬蛋白酶-9 的表達與原發性肝癌侵襲轉移的關系. 胃腸病學和肝病學雜志, 2011, 20(9): 852-854.
10.	Hirano T, Satow R, Kato A, et al. Identification of novel small compounds that restore E-cadherin expression and inhibit tumor cell motility and invasiveness. Biochem Pharmacol, 2013, 86(10): 1419-1429.
11.	Daniele A, Zito AF, Giannelli G, et al. Expression of metalloproteinases MMP-2 and MMP-9 in sentinel lymph node and serum of patients with metastatic and non-metastatic breast cancer. Anticancer Res, 2010, 30(9): 3521-3527.
12.	薛洋, 周清華, 張尚福, 等. MMP-2、MMP-9 在肺癌中的表達及其與肺癌轉移和預后關系的研究. 華西醫學, 2008, 23(2): 225-227.
13.	Peng WJ, Zhang JQ, Wang BX, et al. Prognostic value of matrix metalloproteinase 9 expression in patients with non-small lung cancer. Clin Chim Acta, 2012, 413(13-14): 1121-1126.

1. 陳萬青, 張思維, 鄭榮壽, 等. 中國惡性腫瘤發病和死亡分析. 中國腫瘤, 2013, 22(1): 2-12.
2. 徐煒, 陳清勇, 陳方園. LIMK-1/COFILIN 在姜黃素抑制人肺癌細胞增殖和轉移中的作用. 實用腫瘤雜志, 2014, 29(1): 36-40.
3. Nautiyal J, Banerjee S, Kanwar SS, et al. Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells. Int J Cancer, 2011, 128(2): 951-961.
4. Teiten MH, Gaascht F, Cronauer M, et al. Anti-proliferative potential of curcumin in androgen-dependent prostate cancer cells occurs through modulation of the Wingless signaling pathway. Int J Oncol, 2011, 38(1): 603-611.
5. Mimeault M, Batra SK. Potential application of curcumin and its novel synthetic analogs and nanotechnology-based formulations in cancer prevention and therapy. Chin Med, 2011, 23(1): 31-37.
6. Fan CC, Wang TY, Cheng YA, et al. Expression of E-cadherin, Twist, and P53 and their prognostic value in patients with oral squamous cell carcinoma. J Cancer Res Clin Oncol, 2013, 139(10): 1735-1744.
7. Zhong YC, Zhang T, Di W, et al. Thrombin promotes epithelial ovarian cancer cell invasion by inducing epithelial-mesenchymal transition. J Gynecol Oncol, 2013, 24(3): 265-272.
8. 崔若凡, 張寶剛, 姬靜, 等. ARK5、MMP-2 和 MMP-9 在胃癌中的表達及與侵襲轉移的關系. 實用醫學雜志, 2012, 28(7): 1073-1076.
9. 李登欣, 李石. E-鈣粘素、γ-連環素及基質金屬蛋白酶-9 的表達與原發性肝癌侵襲轉移的關系. 胃腸病學和肝病學雜志, 2011, 20(9): 852-854.
10. Hirano T, Satow R, Kato A, et al. Identification of novel small compounds that restore E-cadherin expression and inhibit tumor cell motility and invasiveness. Biochem Pharmacol, 2013, 86(10): 1419-1429.
11. Daniele A, Zito AF, Giannelli G, et al. Expression of metalloproteinases MMP-2 and MMP-9 in sentinel lymph node and serum of patients with metastatic and non-metastatic breast cancer. Anticancer Res, 2010, 30(9): 3521-3527.
12. 薛洋, 周清華, 張尚福, 等. MMP-2、MMP-9 在肺癌中的表達及其與肺癌轉移和預后關系的研究. 華西醫學, 2008, 23(2): 225-227.
13. Peng WJ, Zhang JQ, Wang BX, et al. Prognostic value of matrix metalloproteinase 9 expression in patients with non-small lung cancer. Clin Chim Acta, 2012, 413(13-14): 1121-1126.

Chinese Journal of Respiratory and Critical Care Medicine

Influence of curcumin in combination with cisplatin on the invasion and metastasis of lung cancer A549 cells and its possible mechanisms

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